FUNCTIONAL DYSPEPSIAseminar.kkh.go.th/downloads/L2 FUNCTIONAL DYSPEPSIA .pdf · FUNCTIONAL...

FUNCTIONAL DYSPEPSIA

Manoon M.

3/9/20

Update management for general practice

Outline

• Dyspepsia

• Uninvestigated dyspepsia (UD)

• Functional dyspepsia (FD)

• Alarm symptoms

• Esophagogastroscopy (EGD)

• Treatment for FD

DYSPEPSIA

•A heterogeneous group of symptoms (pain or discomfort) in the upper abdomen without alarm symptoms for at least 4 weeks.

Thailand Dyspepsia Guidelines 2018

Dyspeptic symptoms

Epigastric pain or burning Belching*

Sensation of fullness Nausea and vomiting

Early satiation Upper abdominal bloating

Anorexia Heartburn and regurgitation

* the most common manifestation in Asian countries


Organic causes of dyspepsia LUMINAL GI TRACT PANCREATICOBILIARY DISORDERS

• Chronic gastric volvulus • Chronic gastric or intestinal ischemia • Food intolerance • Gastric infections (CMV, fungus, tuberculosis,

syphilis) • Gastric or esophageal neoplasms • Gastroesophageal reflux disease • Gastroparesis (diabetes mellitus, postvagotomy,

scleroderma, chronic intestinal pseudo-obstruction, postviral, idiopathic)

• Irritable bowel syndrome • Infiltrative gastric disorders (Ménétrier disease,

Crohn disease, eosinophilic gastroenteritis, sarcoidosis, amyloidosis)

• Parasites (Giardia lamblia, Strongyloides stercoralisrom)

• Peptic ulcer disease

• Biliary pain: cholelithiasis, choledocholithiasis, SOD

• Chronic pancreatitis • Pancreatic neoplasms

SYSTEMIC CONDITIONS

• Adrenal insufficiency • Diabetes mellitus • Heart failure • Hyperparathyroidism • Intra-abdominal malignancy • Myocardial ischemia • Pregnancy • Renal insufficiency • Thyroid disease

Sleisenger and Fordtran’s 11th ed,2021

MEDICATIONS

• Acarbose • Alcohol • Antibiotics, oral (e.g., erythromycin, penicillin,

macrolides) • Aspirin, NSAIDs (including COX-2 selective agents) • Bisphosphonates • CCBs • Colchicine • Corticosteroids • Digitalis preparations • Estrogens • Herbs (e.g., garlic, ginkgo, saw palmetto, feverfew,

chaste tree berry, white willow)

• Iron • Potassium chloride • Levodopa • Metformin • Narcotics • Niacin • Gemfibrozil • Nitrates • Opiates • Orlistat • Quinidine • Sildenafil • Theophylline

Adapted from Loyd RA & McClellan DA .Am Fam Physician 2011 Mar 1;83(5):547-52 Talley NJ, Ford AC. N EnglJ Med 2015;373:1853-63

Sleisenger and Fordtran’s 11th ed,2021

Dyspepsia ควรสงตรวจเพมเตม เมอไหร? ไมเคยเปนมากอน - อาการเขาไดกบdyspepsia? สาเหตทซกประวตพบ? มตวตาเหลอง? มความเสยงโรคหวใจขาดเลอด? ถาไมชดเจนควรตรวจเพมเตม

เคยเปนมากอน รกษาแลวดขน - อาการเหมอนเดม? สาเหตเหมอนเดม? มการใชยาตวใหมๆ/อาหาร/เครองดมทอาจเปนสาเหต? มalarm symptomsไหม?

รกษาแลวไมดขน - เหมอนกลมเคยรกษาแลวดขน และ ประเมนวาใหยาขนาดเหมาะสมแลวหรอไม ใหมานานแคไหนแลว เคยสงตรวจทางหองปฏบตการ/อลตราซาวดชองทองบางหรอไม

UNINVESTIGATED DYSPEPSIA (UD)

• Dyspeptic symptoms in people who have not yet undergone specific diagnostic investigations.


FUNCTIONAL DYSPEPSIA (FD)

• Dyspeptic symptoms cannot be explained by a routine clinical evaluation, including endoscopy, and there is no evidence of Helicobacter pylori infection.

• 2 subcategories:

(1) Postprandial distress syndrome

Postprandial fullness and early satiation (related to meal).

(2) Epigastric pain syndrome

Epigastric pain and epigastric burning (not related to meals).


FUNCTIONAL DYSPEPSIA (FD)

• The worldwide prevalence of UD varies from 7% to 34%, with a pooled UD prevalence from 21 Southeast Asian studies of 21.6%.

• In Asian populations, the risk of malignancy associated with UD is approximately 1.3% (95% CI, 0.80-2.10).

• Secondary dyspepsia was identified in 18% of UD patients after undergoing an endoscopy in Asian countries.

• In Thailand, 60-90% of patients with dyspepsia are eventually diagnosed with FD

• FD is a benign but chronic condition that often fluctuates and is sometimes recurrent.


ALARM FEATURES

• Evidence of upper GI bleeding hematemesis, melena, maroon stool, or iron deficiency without other causes.

• Early satiety.

• Unexplained weight loss (>10% body weight).

• Persistent vomiting due to an unknown cause (defined as vomiting > 10 times in 24 hours or vomiting after each meal).

• Family history of upper GI cancer in a first-degree relative.


ESOPHAGOGASTRODUODENOSCOPY (EGD)

• Dyspeptic patients who have 1 of the following: (1) Age of onset of 50 years or older (2) Alarm features (3) Symptoms are non-responsive to a trial of appropriate medical therapy.


GERD Dyspepsia

(Duration ≥ 4 weeks)

Uninvestigated Investigated

Organic

18%

PUD 11%

Erosive esophagitis 6%

Malignancy 1%

Functional

60-90%

Postprandial distress

syndrome

Epigastric pain syndrome

Alarm symptoms

1) UGIB

2) Early satiety

3) Weight loss (>10%)

4) Vomiting > 10 times in 24 hours or vomiting after each meal

5) Family history of upper GI cancer in a first-degree relative

IBS

Thailand Dyspepsia Guidelines 2018 StanghelliniV., et al. Gastroenterology. 2016 May;150(6):1380-92

Rome IV Criteria for Functional Dyspepsia • Presence of 1 symptom(s) of postprandial fullness, early satiety, epigastric pain, or epigastric burning • No evidence of structural disease that could explain the symptoms

PDS (38%) Postprandial fullness or early satiety 3 days/week for the past 3 months and onset 6 months before diagnosis

EPS (27%) Epigastric pain and/or burning 1 day(s)/week for the past 3 months and onset 6 months before diagnosis

Overlap PDS/EPS 35% Drossman DA, Hasler WL. Gastroenterology. 2016;150(6):1257-1261.

Talley NJ. Korean J Intern Med 2016

Etiology of Functional Dyspepsia

TREATMENT OF FUNCTIONAL DYSPEPSIA

Treatment modalities

• Pharmacotherapy • Acid-Reducing Therapy • Neuromodulators • Prokinetics and Fundus-Relaxing Therapies

• Complementary and Alternative Medicine

• Psychological Therapies

• Helicobacter pylori Eradication

Kimberly N. Harer, et al. Gastroenterology & Hepatology Volume 16, Issue 2 February 2020

Pharmacotherapy Treatment Therapeutic efficacy Quality of

evidence

PPIs Therapeutic gain 7-10% NNT 10-13 Mod

H2RA Therapeutic gain 8-35% NNT 7-13 Low/mod

Prokinetics Therapeutic gain 18-45% NNT 6-7 Low

TCAs, antipsychotics Response rates 64-70% NNT 6 NNH 21

Low

Rebamipide Better than placebo SMD -0.62 Low

SSRI/SNRI = Placebo NNH 6-16 Very low

Antacid, bismuth, sucralfate

= Placebo NA Very low

Lacy BE, et al. Aliment Pharmacol Ther 2012;36:3-15 Ford AC, et al. Gut 2017;66:411-20 Jaafar MH, et al. Dig Dis Sci 2018;63:1250-60

Pinto-Sanchez MI, et al. Cochrane Database Syst Rev 2008 Pittayanon R, et al. Am J Gastroenterol 2018;114:233-243

Moayyedi PM, et al. ACG Guideline 2017

Neuromodulators

• Sulpiride

• Levosulpiride

• Mirtazapine

• Tricyclic antidepressants (TCAs) • Amitriptyline and imipramine

*** Not nortriptyline, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNSIs).

Ford AC, et al. Gut 2017;66:411-420 Kimberly N. Harer, et al. Gastroenterology & Hepatology Volume 16, Issue 2 February 2020

Serotonin Receptor agonist

Pro-kinetic Drug

D2 Receptor antagonist

- Metoclopramide* - Cisapride - Mosapride

- Domperidone - Itopride

* Metoclopramide: action both serotonin agonist and D2 antagonist

Prokinetic agents in Thailand Metoclopramide (Plasil)

Domperidone (Motilium)

Itopride (Ganaton)

Mosapride (Gasmotin)

Mode of action D2 antagonist (5HT4 agonist ) (5HT3 antagonist)

D2 antagonist

D2 antagonist AChE inhibitor

5HT4 agonist

Metabolism pathway CYP450 CYP450 FMO3 CYP450

Prokinetic effects Strong Moderate Strong Strong

Antiemetic effects Strong Moderate-strong Moderate None

QT prolong - + - A case report

Prolactin elevation Rare-moderate Rare-moderate Rare Rare

EPS effects Frequent Rare Rare Rare

Organ selectivity Upper gut Upper gut Upper gut (lower?) Upper and lower gut

ใหยาอยางไร? เมอไหร? เรยกวาตอบสนองหรอไมไดผล


ใหยาอยางไร? เมอไหร? เรยกวาตอบสนองหรอไมไดผล


Omeprazole 20-40mg/day 4-8 weeks

Domperidone 10mg tid or qid ac Mosapride 5mg tid ac

Amitriptyline 25-50 mg/day

Rebamipide 100mg tid ac

Refractory functional dyspepsia

• FD that has continuous symptoms for at least 8 weeks and has been unresponsive to at least 2 medical treatments.*

• The guidelines for FD in the Asia-Pacific region and the United States of America (USA) recommend changing to a different drug if adequate therapeutic efficacy has not been achieved after 4 weeks of treatment.

* Miwa H. et al. J Gastroenterol 2015;50:125-139.

Management of Refractory FD

• H2-RA if PPIs have failed.

• Combination of acid suppression with a prokinetic agent.

• Combination of drug therapy with psychological treatment.

• Adjusting the dose of a TCA, prescribing an antipsychotic drug such as levosulpiride, or adding an anxiolytic.

• The combination of an antidepressant with pregabalin or gabapentin is yet another option that appears to relieve pain.

• Opioids have no therapeutic role and should be avoided because of the risk of dependence.

Neurogastroenterol Motil 2015; 27: 455-67 Am J Gastroenterol 2014; 2: 22-30

หยดยาไดไหม?


หยดยาไดไหม?

ถาอาการดขน คอยๆลดยาลง เชน จาก Multiple drugs single drug

BID dose OD dose วนเวน1-2วน เฉพาะเวลามอาการ

ภายใน 6-12 เดอน


โรคนจะหายไหม?

• All FD patients should be offered a positive diagnosis after targeted investigation

• Attention to stress reduction and lowering of anxiety is important

50% Resolution of symptoms

30-35% Symptoms fluctuate and/or meet criteria for another FGIDs

15-20% Persistent symptoms

No evidence to suggest that it is associated with decreased survival

Talley NJ, Ford AC. N Engl J Med 2015;373:1853-63

อย รพช. เมอไหร? ควรสงตอพบแพทยเฉพาะทาง


อย รพช. ควรสงตอพบแพทยเฉพาะทางเมอไหร?


หาม/แนะน าการรบประทานอาหาร,เครองดมอยางไรบาง?

Dietary recommendations for patients with functional dyspepsia.

• Eat slowly and regularly.

• Decrease fat intake.

• Try to observe a diet that is more similar to a Mediterranean diet or increase

the intake of fresh foods and decrease the intake of ultra-processed foods.

• Decrease coffee and alcohol consumption.

• A gluten-free diet and a low-FODMAPs diet could be tested over a short time

period (4–8 weeks) and must be stopped if there is no efficacy.

• Be careful in providing strong recommendations to obsessive patients, and

avoid the recommendation of very restrictive diets.

Duboc et al. Front. Psychiatry, 05 February 2020

หาม/แนะน าการรบประทานอาหาร,เครองดมอยางไรบาง?

Dietary recommendations for patients with functional dyspepsia.

• Eat slowly and regularly.

• Decrease fat intake.

• Try to observe a diet that is more similar to a Mediterranean diet or increase

the intake of fresh foods and decrease the intake of ultra-processed foods.

• Decrease coffee and alcohol consumption.

• A gluten-free diet and a low-FODMAPs diet could be tested over a short time

period (4–8 weeks) and must be stopped if there is no efficacy.

• Be careful in providing strong recommendations to obsessive patients, and

avoid the recommendation of very restrictive diets.

Duboc et al. Front. Psychiatry, 05 February 2020

รบประทานชาๆ เนอสตวไมผานการปรงแตง เนนผกผลไม ไมมน ไมหวาน ไมหมกดอง งดกาแฟและแอลกอฮอล

สมนไพร/อาหารเสรม ทชวยใหดขนมไหม?

• Peppermint

• Ginger (ขง)

• STW5

• FDgard

• Turmeric (ขมนชน)

THANK YOU

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